BUSCADOR RECOLECTA

Dades primàries associades a l'article publicat a PLoS Neglected Tropical Diseases, vol. 10, num. 10, p. e0005009 [http://dx.doi.org/10.1371/journal.pntd.0005009], P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, p<0.5). Peripheral blood mononuclear cells from PNG uninfected pregnant women had significantly higher antigen-specific IFN-g TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.5). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings.

Dades primàries associades a l'article publicat a Plos Neglected Tropical Diseases, vol. 14, num. 5, p. e0008155 [https://doi.org/10.1371/journal.pntd.0008155], Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and delivery (periphery, cord and placenta), allowing a longitudinal analysis. At recruitment, we found that P. vivax–infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1β, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL-10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition.

Study of immune correlates against malaria after vaccination with RTS,S/ASO1E: a comphrensive immunological arm of a Phase III double-blind, randomize, controlled multi-centre trial (MAL067)., Dades primàries associades a l'article publicat a NPJ Vaccines, vol. 5 [https://doi.org/10.1038/s41541-020-0192-7], The RTS,S/AS01E vaccine has shown consistent but partial vaccine efficacy in a pediatric phase 3 26 clinical trial using a 3-dose immunization schedule. A fourth dose 18 months after the primary 27 vaccination was shown to restore the waning efficacy. However, only total IgG against the 28 immunodominant malaria vaccine epitope has been analyzed following the booster. To better 29 characterize the magnitude, nature and longevity of the immune response to the booster, we 30 measured levels of total IgM, IgG and IgG1-4 subclasses against three constructs of the 31 circumsporozoite protein (CSP) and the hepatitis B surface antigen (HBsAg, also present in RTS,S) 32 by quantitative suspension array technology in 50 subjects in the phase 3 trial in Manhiça, 33 Mozambique. To explore the impact of vaccination on naturally acquired immune responses, we 34 measured antibodies to P. falciparum antigens not included in RTS,S. We found increased IgG, 35 IgG1, IgG3 and IgG4, but not IgG2 nor IgM, levels against vaccine antigens one month after the 4th 36 dose. Overall, antibody responses to the booster dose were lower than the initial peak 37 response to primary immunization and children had higher IgG and IgG1 levels than infants. 38 Higher anti-Rh5 IgG and IgG1-4 levels were detected after the booster dose, suggesting that RTS,S 39 partial protection could increase some blood stage antibody responses. Our work shows that the 40 response to the RTS,S/AS01E booster dose is different from the primary vaccine immune 41 response and highlights the dynamic changes in subclass antibody patterns upon the vaccine 42 booster and with acquisition of adaptive immunity to malaria.

Dades primàries associades a l'article publicat a EClinicalMedicine, vol. 32 [https://doi.org./10.1016/j.eclinm.2020.100720], The trial was conducted in the Pamplona metropolitan area (Navarra, Spain). Patients were enrolled between July 31, 2020 and September 11, 2020 and randomized in a 1:1 ratio to ivermectin (400 mcg/kg) single oral dose or placebo. Assessments on enrollment and at days 4, 7, 14, 21 and 28 post treatment included: general symptoms report, physical examination and adverse events. All patients were asked to complete a daily online diary of symptoms from day 1 to 28 post treatment. On enrollment, as well as on days 7 and 14 blood samples were obtained to assess full blood count, C reactive protein, procalcitonin, ferritin, creatinine phosphokinase, lactic dehydrogenase, troponin T, D dimer, IL-6, and renal function. Viral loads were calculated at enrollment and on days 4, 7, 14 and 21 post treatment based on a nasopharyngeal swab for SARS-CoV-2 PCR (for genes N and E). A semi-quantitative serology for IgG against SARS-CoV-2 was done on samples from all patients on day 21 post-treatment.